Anxiety-like (a, b) and depressive-like (c, d) behaviours were measured during the day (ZT 6-10) and night (ZT 18-22) in wild-type (WT) and ClockΔ19 mutant mice. (a) ClockΔ19 mutant mice exhibited a significant increase in entries into the centre of the open field during the day (main effect of genotype, F1,28=11.72, p=0.0019; post-hoc, p<0.01) that decreased to WT levels at night (genotype by time interaction, F1,28=4.19, p=0.05). ClockΔ19 mice also spent more time in the centre of the open field during the day (main effect of genotype, F1,28=6.17, p=0.02; post-hoc, p<0.05) with differences no longer apparent at night.(b) This daytime specific anxiolytic profile was also found in the light-dark test, where ClockΔ19 mice entered the light chamber significantly more than WT controls during the day (main effect of genotype, F1,28=4.23, p=0.049; post-hoc, p<0.05) but significantly decreased exploration to WT levels at night (genotype by time interaction, F1,28=5.35, p=0.03; post-hoc student’s t-test, p=0.06, ClockΔ19 day vs. night). ClockΔ19 mice also spent more time in the light chamber of the light/dark box during the day (main effect of genotype, F1,28=4.29, p=0.048; post-hoc, p<0.05), with a significant decrease to WT levels at night (genotype by time interaction, F1,28=5.03, p=0.03; post-hoc student’s t-test, p=0.049, ClockΔ19 day vs. night). (c) ClockΔ19 mice exhibited decreased depressive-like behaviors during the day as evidenced by increased struggling time in the forced swim test (main effect of genotype, F1,28=44.7, p<0.0001; post-hoc, p<0.0001) and (d) an increased preference for a 1% sucrose solution (main effect of genotype F1,27=5.46, p=0.027; post-hoc, p<0.05). Differences in depressive-like behaviours were no longer evident at night as ClockΔ19mutant mice significantly decreased struggling time to near WT levels in the forced swim test (c:genotype by time interaction, F1,28=7.84, p=0.0092; post-hoc, p<0.0001) and no longer showed a preference for sucrose relative to WT mice (d). Day and night cohorts, n=8–9/group.